A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients
9 de diciembre de 2020 actualizado por: Novartis Pharmaceuticals
A Multi-part, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Efficacy of Tropifexor (LJN452) in Patients With Primary Biliary Cholangitis
A multi-part study to assess safety, tolerability and efficacy of tropifexor (LJN452) in patients with primary biliary cholangitis
Descripción general del estudio
Estado
Terminado
Condiciones
Tipo de estudio
Intervencionista
Inscripción (Actual)
61
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
-
-
-
Hamburg, Alemania, 20246
- Novartis Investigative Site
-
Hannover, Alemania, 30625
- Novartis Investigative Site
-
Heidelberg, Alemania, 69120
- Novartis Investigative Site
-
Muenchen, Alemania, 81377
- Novartis Investigative Site
-
Wuerzburg, Alemania, 97080
- Novartis Investigative Site
-
-
-
-
Alberta
-
Calgary, Alberta, Canadá, T2N 4N1
- Novartis Investigative Site
-
Edmonton, Alberta, Canadá, T6G 2B7
- Novartis Investigative Site
-
-
-
-
California
-
Rialto, California, Estados Unidos, 92377
- Novartis Investigative Site
-
-
Florida
-
Miami, Florida, Estados Unidos, 33136
- Novartis Investigative Site
-
-
Georgia
-
Atlanta, Georgia, Estados Unidos, 30308
- Novartis Investigative Site
-
Marietta, Georgia, Estados Unidos, 30060
- Novartis Investigative Site
-
-
Illinois
-
Chicago, Illinois, Estados Unidos, 60612
- Novartis Investigative Site
-
-
New York
-
Manhasset, New York, Estados Unidos, 11030
- Novartis Investigative Site
-
-
Texas
-
Dallas, Texas, Estados Unidos, 75390
- Novartis Investigative Site
-
San Antonio, Texas, Estados Unidos, 78215
- Novartis Investigative Site
-
-
Washington
-
Seattle, Washington, Estados Unidos, 98104
- Novartis Investigative Site
-
-
-
-
-
Moscow, Federación Rusa, 117198
- Novartis Investigative Site
-
Saint-Petersburg, Federación Rusa, 194044
- Novartis Investigative Site
-
Samara, Federación Rusa, 443011
- Novartis Investigative Site
-
-
-
-
-
Lodz, Polonia, 91-347
- Novartis Investigative Site
-
Myslowice, Polonia, 41-400
- Novartis Investigative Site
-
Warsaw, Polonia, 02-097
- Novartis Investigative Site
-
Wroclaw, Polonia, 50-449
- Novartis Investigative Site
-
-
-
-
-
Cambridge, Reino Unido, CB2 2QQ
- Novartis Investigative Site
-
Hull, Reino Unido, HU3 2JZ
- Novartis Investigative Site
-
London, Reino Unido, NW3 2PF
- Novartis Investigative Site
-
Newcastle upon Tyne, Reino Unido, NE1 4LP
- Novartis Investigative Site
-
-
West Midlands
-
Birmingham, West Midlands, Reino Unido, B15 2TH
- Novartis Investigative Site
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Age ≥ 18 years
Diagnosis of PBC as demonstrated by the presence of at least 2 of the following 3 diagnostic criteria:
- History of alkaline phosphatase (ALP) elevated above upper limit of normal (ULN) for at least 6 months
- Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low titer (<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components (PDC-E2, 2-oxo-glutaric acid dehydrogenase complex))
- Previous liver biopsy findings consistent with PBC
At least 1 of the following markers of disease severity:
- ALP ≥ 1.67 × ULN
- Total bilirubin > ULN but < 1.5 × ULN
In addition, patients must meet the following biochemical criteria at enrollment:
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 × ULN
- Total bilirubin ≤ 1.5 × ULN
- INR ≤ ULN
- Taking UDCA for at least 12 months, or for at least 6 months and has reached maximal response to UDCA with a plateau in alkaline phosphatase, with no changes in dose for ≥ 3 months prior to Day 1.
- Patients must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 40 kg/m2. BMI = Body weight (kg) / [Height (m)]2
Exclusion Criteria:
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception for 30 days before randomization, during dosing and for 30 days following the end of treatment.
Presence of other concomitant liver diseases.
- Cirrhosis with complications, including history or presence of:
- Variceal bleed
- Uncontrolled ascites
- Encephalopathy
- Spontaneous bacterial peritonitis
- Significant hepatic impairment as defined by Child-Pugh classification of B or C, history of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥15.
- History of conditions that may cause increases in ALP (e.g., Paget's disease).
- Use of investigational drugs, or immunosuppressive drugs at the time of enrollment, or within 5 half-lives, or 30 days of randomization, whichever is longer; or longer if required by local regulations. Use of high dose oral steroids to treat co-morbid conditions (e.g., airways disease) will be allowed but must be properly documented as such in concomitant medications.
- Currently taking obeticholic acid or have taken obeticholic acid within 30 days of randomization
- Previous participation in CLJN452X2201 and received study medication within three months of randomization (or longer if required by local regulations).
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Comparador de placebos: Placebo
|
Matching placebo capsules administered once daily for 28 days
Matching placebo to LJN452 administered once a day for 12 weeks
|
|
Experimental: LJN452
|
LJN452 capsules administered once daily for 28 days
Otros nombres:
LJN452 capsules administered once a day for 12 weeks
Otros nombres:
LJN452
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Fold Change in Serum Gamma-glutamyl Transferase (GGT)
Periodo de tiempo: Baseline to Day 28
|
Fold change in serum gamma-glutamyl transferase (GGT) from baseline to Day 28
|
Baseline to Day 28
|
|
Blood Pressure
Periodo de tiempo: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
|
Vital signs - Systolic Blood pressure
|
Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
|
|
Pulse Rate
Periodo de tiempo: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
|
Vital signs
|
Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
|
|
Body Temperature
Periodo de tiempo: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
|
Vital signs
|
Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
|
|
ECG - Heart Rate
Periodo de tiempo: Screening, Baseline, day 1, day 28
|
Electrocardiogram (ECG)
|
Screening, Baseline, day 1, day 28
|
|
ECG Intervals - PR Interval
Periodo de tiempo: Screening, Baseline, day 1, day 28
|
Electrocardiogram (ECG)
|
Screening, Baseline, day 1, day 28
|
|
Haemoglobin
Periodo de tiempo: Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
|
Hematology panel for safety laboratory assessments.
|
Screening, Baseline, day 1, day 7, day 14, day 21, day 28, day 56, day 84
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Plasma PK Parameter - AUC 0-8h
Periodo de tiempo: Day 1, Day 28
|
Tropifexor levels were determined in plasma using a validated LC-MS/MS method.
AUC0-t=The area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration [mass x time / volume]
|
Day 1, Day 28
|
|
Plasma PK Parameter - Cmax
Periodo de tiempo: Day 1, Day 28
|
Tropifexor levels were determined in plasma using a validated LC-MS/MS method.
Cmax=The observed maximum plasma concentration following drug administration [mass /volume]
|
Day 1, Day 28
|
|
Plasma PK Parameter - Tmax
Periodo de tiempo: Day 1, Day 28
|
Tropifexor levels were determined in plasma using a validated LC-MS/MS method.
Tmax = The time to reach the maximum concentration after drug administration [time]
|
Day 1, Day 28
|
|
Changes From Baseline in Total PBC-40 Score
Periodo de tiempo: Baseline, Day 28, Day 56, Day 84
|
Baseline is defined as the latest available predose value.
The PBC-40 is a paper-based, patient-derived, disease-specific health-related quality of life (HRQOL) patient reported outcome (PRO) measure which was developed and validated for use in PBC patients (Jacoby et al 2005).
It consists of 40 questions arranged in 6 domains with between 3 and 11 questions in each domain.
Each question is scored from 1 to 5 in increasing order of severity.
All questions within a domain are summed and all domain totals are summed to obtain a total score.
The total score range is between a minimum of 40 and a maximum of 200.
Higher scores represent a poorer quality of life.
The median difference from baseline in total sum score for each treatment group is presented.
|
Baseline, Day 28, Day 56, Day 84
|
|
Change From Baseline in Itch Subdomain of PBC-40 Score
Periodo de tiempo: Baseline, Day 28, Day 56, Day 84
|
Baseline is defined as the latest available predose value.
The PBC-40 is a paper-based, patient-derived, disease-specific health-related quality of life (HRQOL) patient reported outcome (PRO) measure which was developed and validated for use in PBC patients (Jacoby et al 2005).
It consists of 40 questions arranged in 6 domains with between 3 and 11 questions in each domain.
Each question is scored from 1 to 5 in increasing order of severity.
This dataset focuses on the itch subdomain which consists of 3 questions.
These 3 questions within the itch subdomain are summed to obtain a total score for the itch subdomain.
The total score range is between a minimum of 3 and a maximum of 15.
Higher scores represent a poorer quality of life.
The median change from baseline in total itch subdomain score in each treatment group is presented.
|
Baseline, Day 28, Day 56, Day 84
|
|
Change From Baseline in Global Itch Visual Analogue Scale (VAS)
Periodo de tiempo: Day 7, Day 14, Day 21, Day 28, Day 56, and Day 84
|
Baseline is defined as the latest available predose value.
The Global Itch Visual Analogue Scale, a 100 mm visual analogue scale (VAS), was used to assess the severity of patients itch (ranging from 0 = none at all to 100 = the worst imaginable itch).
The score range is between a minimum of 0 and a maximum of 100.
The score (distance in mm from left) on the VAS was recorded by the patient marking with a line and used to test for an effect of tropifexor over placebo.
The mean change from baseline in itch VAS score in each treatment group is presented.
|
Day 7, Day 14, Day 21, Day 28, Day 56, and Day 84
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
9 de septiembre de 2015
Finalización primaria (Actual)
2 de agosto de 2018
Finalización del estudio (Actual)
2 de agosto de 2018
Fechas de registro del estudio
Enviado por primera vez
4 de agosto de 2015
Primero enviado que cumplió con los criterios de control de calidad
4 de agosto de 2015
Publicado por primera vez (Estimar)
6 de agosto de 2015
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
5 de enero de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
9 de diciembre de 2020
Última verificación
1 de octubre de 2019
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- CLJN452X2201
- 2015-001590-41 (Número EudraCT)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Sí
Descripción del plan IPD
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .